INVESTIGADORES
MILANESI Lorena Magdalena
congresos y reuniones científicas
Título:
THE ANTIAPOPTOTIC EFFECT OF 17©¬-ESTRADIOL IN SKELETAL MUSCLE CELLS INVOLVES PKC¥ä, JNK AND p66Shc
Autor/es:
LA COLLA, ANABELA; PRONSATO, LUCÍA; MILANESI, LORENA; BOLAND, RICARDO; VASCONSUELO, ANDREA
Lugar:
Bs As
Reunión:
Congreso; Reuniòn anual de AAOMM; 2014
Institución organizadora:
AAOMM
Resumen:
The hormone 17¥â-Estradiol
(E2) acts on several non-reproductive tissues, including skeletal muscle. We
have shown that E2 at physiological concentrations prevented apoptosis induced
by hydrogen peroxide (H2O2) in skeletal
myoblasts. The present work further characterizes the signaling mechanisms
modulated by E2, responsible of apoptosis inhibition inskeletal muscle cells. We found that H2O2
induces activation of PKC¥ä and
JNK in C2C12 cells. By TUNEL assays using specific inhibitors, we demonstrated
that the H2O2-induced activation of PKC¥ä and JNK are
necessary to trigger apoptosis in skeletal muscle cells.
Moreover, immunological assays support the data that PKC¥ä acts upstream JNK. We observed that
E2 inhibits the activation of these kinases, resulting in the
inhibition of phosphorylation and
translocation to mitochondria
of the adaptor protein p66Shc associated to oxidative
stress. Additionally, we
found that E2 diminishes the H2O2-induced p66Shc messenger
RNA (mRNA) level. Tetramethylrhodamine
methyl ester (TMRM) staining showed that pretreatment with E2 conduces to protection
of the mitochondrial membrane potential (∆¥÷m) in line with the inhibition of p66Shc translocation to mitochondria.
In agreement, by qRT-PCR we demonstrated that E2 diminishes the H2O2-induced
mRNA levels of the apoptotic proteins PERP and Puma associated to ∆¥÷m loss, and increases those of the antiapoptotic
protein Bcl-2. Our results provide basis for a putative
mechanism by which E2 exerts beneficial effects on mitochondria, against
oxidative stress, in skeletal muscle cells, helping to find new targets for the
development of therapies for myophaties associated to deregulated apoptosis by
hormonal deficits.